Expression of transforming growth factor-beta (TGF-beta) was examined in cultured human lung cancer cells at the level of mRNA and protein. Specific cDNA probes and antibodies for TGF-betas 1, 2 and 3 were used to study expression of these isoforms in both non-small cell lung cancer (NSCLC) cells and small cell lung cancer (SCLC) cells. Expression of TGF-beta1 mRNA was detected in both cell types using Northern blot hybridization, with expression being generally higher in NSCLC cells. Furthermore, expression of TGF-beta1 mRNA was higher than that of the mRNAs for TGF-betas 2 and 3 in these cells. Immunohistochemical staining of cultured lung cancer cells with TGF-beta antibodies showed immunoreactive TGF-betas 1, 2 and 3 proteins. Our results demonstrate coordinate expression of these TGF-beta1 mRNA and protein more prominent than that of TGF-betas 2 and 3. Expression of both the mRNAs and proteins of the three TGF-beta isoforms was differentially affected upon incubation with retinoic acid in some NSCLC cells. In addition, growth of some NSCLC cells in soft agar was inhibited after incubation with retinoic acid. The significance of the project is to determine whether expression of one or more of the TGF-beta isoforms can be increased in lung cancer cells by treatment with agents such as retinoic acid so that increased TGF-beta production may be able to be used as a potential therapeutic agent to control their proliferation.